Malaria is a particular problem in pregnancy because of enhanced sensitivity, the possibility of placental malaria, and adverse effects on pregnancy outcome. Artemisinin‐containing combination therapies (ACTs) are the most effective antimalarials known. WHO recommends 7‐day quinine therapy for uncomplicated Plasmodium falciparum malaria in the first trimester despite the superior tolerability and efficacy of 3‐day ACT regimens because artemisinins caused embryolethality and/or cardiovascular malformations at relatively low doses in rats, rabbits, and monkeys. The developmental toxicity of artesunate, artemether, and DHA were similar in rats but artesunate was embryotoxic at lower doses in rabbits (5 mg/kg/day) than artemether (no effect level = 25 mg/kg/day). In clinical studies in Africa, treatment with artemether–lumefantrine in the first trimester was observed to be highly efficacious and the miscarriage rate (≤3.1%) was similar to no antimalarial treatment (2.6%). When data from the first‐trimester use of largely artesunate‐based therapies in Thailand were pooled together, there was no difference in miscarriage rate compared to quinine. However, individually, artesunate–mefloquine was associated with a higher miscarriage rate (15/71 = 21%) compared to other artemisinin‐based therapies including 7‐day artesunate + clindamycin (2/50 = 4%) and quinine (92/842 = 11%). Thus, appropriate statistical comparisons of individual ACT groups are needed prior to assuming that they all have the same risk for developmental toxicity. Current limitations in the assessment of the safety of ACTs in the first trimester are a lack of exposures early in gestation (gestational weeks 6–7), limited postnatal evaluation for cardiovascular malformations, and the pooling of all ACTs for the assessment of risk.

中文翻译：

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致畸剂更新：妊娠期疟疾和妊娠早期抗疟药物的使用

疟疾是妊娠期的一个特殊问题，因为它具有更高的敏感性、胎盘疟疾的可能性以及对妊娠结果的不利影响。含青蒿素的联合疗法 (ACTs) 是已知的最有效的抗疟药。世卫组织建议对无并发症的恶性疟原虫进行 7 天奎宁治疗尽管 3 天 ACT 方案具有更好的耐受性和有效性，但由于青蒿素在大鼠、兔子和猴子中以相对较低的剂量引起胚胎死亡和/或心血管畸形，因此在孕早期仍会出现疟疾。青蒿琥酯、蒿甲醚和 DHA 在大鼠中的发育毒性相似，但青蒿琥酯在兔体内的剂量（5 毫克/公斤/天）比蒿甲醚（无影响水平 = 25 毫克/公斤/天）时具有胚胎毒性。在非洲的临床研究中，观察到在妊娠早期使用蒿甲醚-苯芴醇治疗非常有效，流产率 (≤3.1%) 与未进行抗疟治疗 (2.6%) 相似。将泰国在妊娠早期使用的主要以青蒿琥酯为基础的疗法的数据汇总在一起时，与奎宁相比，流产率没有差异。然而，个人而言，与包括 7 天青蒿琥酯 + 克林霉素 (2/50 = 4%) 和奎宁 (92/842 = 11%) 在内的其他基于青蒿素的疗法相比，青蒿琥酯-甲氟喹与更高的流产率 (15/71 = 21%) 相关. 因此，在假设它们都具有相同的发育毒性风险之前，需要对各个 ACT 组进行适当的统计比较。目前在妊娠早期评估 ACT 安全性的局限性是在妊娠早期（妊娠 6-7 周）缺乏暴露，对心血管畸形的产后评估有限，以及汇集所有 ACT 用于风险评估。在假设它们都具有相同的发育毒性风险之前，需要对各个 ACT 组进行适当的统计比较。目前在妊娠早期评估 ACT 安全性的局限性是在妊娠早期（妊娠 6-7 周）缺乏暴露，对心血管畸形的产后评估有限，以及汇集所有 ACT 用于风险评估。在假设它们都具有相同的发育毒性风险之前，需要对各个 ACT 组进行适当的统计比较。目前在妊娠早期评估 ACT 安全性的局限性是在妊娠早期（妊娠 6-7 周）缺乏暴露，对心血管畸形的产后评估有限，以及汇集所有 ACT 用于风险评估。